MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR
Metrics: PDF 885 views | HTML 1730 views | ?
Claudia J. Krause1,3, Oliver Popp2, Nanthakumar Thirunarayanan1, Gunnar Dittmar2, Martin Lipp1, Gerd Müller1
1Molecular Tumor Genetics and Immunogenetics, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
2Mass Spectrometry Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
3Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Gerd Müller, e-mail: firstname.lastname@example.org
Claudia J. Krause, e-mail: email@example.com
Martin Lipp, e-mail: mLipp@mdc-berlin.de
Keywords: KSHV, vGPCR, microRNA-34a, genomic instability, genome maintenance mechanisms
Received: August 13, 2015 Accepted: January 17, 2016 Published: February 8, 2016
The Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi’s sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR–induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.